This project has developed a clinically-useful method (laser Doppler instrument and its theory of operation) for clinical measurements of microcirculatory blood flow, number density of flowing red blood cells (RBCs), and mean RBC velocity. Assistance has been given to the commercialization of this methodology and its application to clinical research in many laboratories worldwide. Our clinical studies have been directed toward examining normal and abnormal microvascular dynamics through noninvasive clinical studies of skin and nasal mucosa, and in intra-operative clinical studies of muscle and CNS. Collaboration with USUHS is directed toward developing endoscopic application of this technology. Considerable theoretical work has been directed toward an adequate construct with which to interpret the physical measurements and refining the accuracy of the microcirculatory measurements. We have discovered abnormal microcirculatory patterns and responses in the skin of patients with sickle cell disease, hypertension, certain cardiac circulatory syndromes, diabetes, and skin cancer. The microcirculatory effects of therapy are monitored with this technique, affording a better understanding of the microcirculatory component of these diseases.